In two recent randomized clinical trials studying tocilizumab in patients with systemic sclerosis, a weekly regimen of 162 mg was more effective than placebo in preserving predicted forced vital capacity at 24 and 48 weeks, according to an expert at the annual Basic and Clinical Immunology for the Busy Clinician symposium, in Scottsdale, Arizona.
“These were small studies, but there were dramatic findings,” Vibeke Strand, MD, MACR, FACP, a biopharmaceutical consultant and clinical rheumatologist based in Portola Valley, California, told attendees. “They were the phase 2 FaSScinate study, and then the phase 3 FocuSSced study.”
In the phase 2 FaSScinate study, which was published in The Lancet in 2016, Dinesh Khanna, MD, of the University of Michigan, and colleagues, enrolled 87 patients with diffuse SSc from 35 hospitals in Canada, France, Germany, the United Kingdom and the United States. All participants had five or fewer years of disease duration from first non-Raynaud's sign or symptom, with 43 randomly assigned to receive weekly 162-mg doses of tocilizumab (Actemra, Genentech) and 44 assigned to placebo. The primary endpoint was the difference in mean change from baseline in modified Rodnan skin score at 24 weeks.
Tocilizumab is more effective than placebo in preserving predicted forced vital capacity at 24 and 48 weeks, according to an expert.
According to Strand, although the primary endpoint related to modified Rodnan skin score was not met, there was nonetheless a statistically significant improvement in forced vital capacity among patients treated with tocilizumab (P = .037). Decreased forced vital capacity was –34 mL among patients treated with tocilizumab, and –171 mL in the placebo group (P = .0368), Strand said. Meanwhile, 33% of patients in the tocilizumab group and 34% who received placebo experienced serious adverse events.
In the phase-3 FocuSSced study, presented at the American College of Rheumatology 2018 Annual Meeting in Chicago by Khanna, 210 patients with SSc were randomly assigned to receive either 162 mg of tocilizumab or placebo each week for 48 weeks. Once again, the primary endpoint was difference in mean change in modified Rodman skin score, from baseline to week 48. Secondary endpoints were change from baseline in percent predicted forced vital capacity at week 48 and time to treatment failure.
According to Strand, the primary outcome related to modified Rodman skin score was once again not met. However, tocilizumab performed better than placebo in cumulative distribution of change in percent predicted forced vital capacity (P = .0015). The mean change difference in forced vital capacity, from baseline to week 48, was 167 mL, with tocilizumab performing better than placebo (95% CI, 83-250).
“In two replicant trials, tocilizumab weekly was more effective than placebo, in terms of percent predicted forced vital capacity at 24 and 48 weeks,” Strand said. “Clinically meaningful progression was defined as a greater than 10% decline in forced vital capacity, or a 5% to 10% relative decline in capacity, with a 15% or greater decline in diffusing capacity of the lungs for carbon monoxide.”
She noted, “I don’t think most of us believe that modified Rodman skin score is sufficient as an outcome for systemic sclerosis, but we will have to continue to work on this, and as much as it may have some indications in Raynaud’s syndrome and other conditions, it does not necessarily reflect internal organ development.” – by Jason Laday
- Stand V. What’s new with IL-6 Inhibitors; Feb. 15-16, 2019; Scottsdale, Ariz.
- Khanna D, et al. Lancet. 2016;doi:10.1016/S0140-6736(16)00232-4.
- Khanna D, et al. Abstract 898. Presented at: ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.
Disclosure: Healio Rheumatology was unable to determine Strand’s relevant financial disclosures.